High Resolution Triple Quadrupole Mass Spectrometer: Funds are requested from the Division of Research Resources for the purchase of Thermo Finnigan TSQ Quantum Ultra AM high-resolution triple quadrupole MS/MS system. Until the development this instrument, no high-resolution triple quadrupole mass spectrometers have been available. The use of conventional triple quadrupole instruments has become an important tool in laboratories that are engaged in biomarker research using quantitative mass spectrometry. However, it is becoming recognized that the ability to analyze molecules in the electron capture mode atmospheric pressure chemical ionization (APCI) mode that we discovered several years ago offers significant advantages when compared with conventional ionization methods for the analysis of endogenous compounds. In fact over thirty applications of this methodology have already cited our original discovery. The ability to conduct analyses with high resolution and high sensitivity provides an additional advantage over conventional triple quadrupole methodology. The new Ion Max source in this instrument has interchangeable electrospray ionization (ESI) and APCI probes, a titanium skimmer with hard-edged skimming, and larger aperture for increase robustness and sensitivity. It has a redesigned ion transfer tube lens with wider aperture for enhanced ion focusing and ion transmission. The "Ion Max" source also allows full probe adjustment in the x, y, and z directions with two view ports and a quick release probe lever. The probe position can be optimized for maximum robustness and sensitivity with any given combination of flow rate, solvent, and ionization mode. Its new, ultra high temperature, self-cleaning APCI probe, with ceramic heater, virtually eliminates carryover. The Finnigan TSQ Quantum Ultra's innovative technology provides the widest linear dynamic range and lowest sensitivity 1imits o f any triple quadrupole mass spectrometer on the market (5-6 orders of magnitude). The instrument has the powerful capability of routine accurate mass measurements on the chromatographic timescale. Its redesigned analyzer control circuitry allows full advantage to be taken of the high-resolution HyperQuad mass analyzers. This makes it possible to conduct high-resolution analyses with minimal loss of sensitivity. The use of electron capture APCI coupled with high resolution and high sensitivity offers unique capabilities for lipid, DNA, and protein biomarkers of oxidative stress. The Thermo Finnigan TSQ Quantum Ultra AM LC/MS/MS System represents the current state-of-the-art in commercial instruments with electron capture APCI capabilities. A major user group consisting of five NIH-funded investigators would use the instrument to perform biomarker research. A minor user group consisting of five NIH-funded investigators would also conduct research using the instrument. An occasional user group of ten NIH-funded investigators would use the instrument for most of the remaining instrument time. It is estimated that over five years, the instrument would benefit the research programs of an additional 20-30 investigators. Therefore, the new instrument would impact significantly on research programs of some 40-50 NIH-funded investigators at the University of Pennsylvania. [unreadable] [unreadable]